Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime
We investigated the effects of the antibiotic ceftazidime (CAZ) on the cytolytic action of the neutrophil myeloperoxidase–hydrogen peroxide–chloride anion system (MPO/H2O2/Cl−). In this system, myeloperoxidase catalyses the conversion of H2O2 and CI− to the cytotoxic agent HOCl. Stimulated neutrophi...
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| Format: | Article |
| Language: | English |
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Wiley
1995-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/S0962935195000706 |
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| author | M. Mathy-Hartert G. Deby-Dupont C. Deby L. Jadoul A. Vandenberghe M. Lamy |
| author_facet | M. Mathy-Hartert G. Deby-Dupont C. Deby L. Jadoul A. Vandenberghe M. Lamy |
| author_sort | M. Mathy-Hartert |
| collection | DOAJ |
| description | We investigated the effects of the antibiotic ceftazidime (CAZ) on the cytolytic action of the neutrophil myeloperoxidase–hydrogen peroxide–chloride anion system (MPO/H2O2/Cl−). In this system, myeloperoxidase catalyses the conversion of H2O2 and CI− to the cytotoxic agent HOCl. Stimulated neutrophils can release MPO into the extracellular environment and then may cause tissue injury through direct endothelial cells lysis. We showed that human umbilical vein endothelial cells (HUVEC) were capable of taking up active MPO. In presence of H2O2 (10−4 M), this uptake was accompanied by cell lysis. The cytolysis was estimated by the release of 51Cr from HUVEC and expressed as an index of cytotoxicity (IC). Dose dependent protection was obtained for CAZ concentrations ranging from 10−5 to 10−3 M;this can be attributed to inactivation of HOCl by the drug. This protection is comparable to that obtained with methionine and histidine, both of which are known to neutralize HOCl. This protection by CAZ could also be attributed to inactivation of H2O2, but when cytolysis was achieved with H2O2 or O2− generating enzymatic systems, no protection by CAZ was observed. Moreover, the peroxidation activity of MPO (action on H2O2) was not affected by CAZ, while CAZ prevented the chlorination activity of MPO (chlorination of monochlorodimedon). So, we concluded that CAZ acts via HOCl inactivation. These antioxidant properties of CAZ may be clinically useful in pathological situations where excessive activation of neutrophils occurs, such as in sepsis. |
| format | Article |
| id | doaj-art-004454aed3c640bc9aba436d69539d37 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 1995-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-004454aed3c640bc9aba436d69539d372025-02-03T05:59:55ZengWileyMediators of Inflammation0962-93511466-18611995-01-014643744310.1155/S0962935195000706Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidimeM. Mathy-Hartert0G. Deby-Dupont1C. Deby2L. Jadoul3A. Vandenberghe4M. Lamy5Centre for the Biochemistry of Oxygen, Institut de Chimie, B6, Université de Liège, Domaine Universitaire du Sart Tilman, Liège 4000, BelgiumCentre for the Biochemistry of Oxygen, Institut de Chimie, B6, Université de Liège, Domaine Universitaire du Sart Tilman, Liège 4000, BelgiumCentre for the Biochemistry of Oxygen, Institut de Chimie, B6, Université de Liège, Domaine Universitaire du Sart Tilman, Liège 4000, BelgiumGlaxo Belgium sa, Boulevard du Triomphe, 172, Bruxelles, BelgiumGlaxo Belgium sa, Boulevard du Triomphe, 172, Bruxelles, BelgiumCentre for the Biochemistry of Oxygen, Institut de Chimie, B6, Université de Liège, Domaine Universitaire du Sart Tilman, Liège 4000, BelgiumWe investigated the effects of the antibiotic ceftazidime (CAZ) on the cytolytic action of the neutrophil myeloperoxidase–hydrogen peroxide–chloride anion system (MPO/H2O2/Cl−). In this system, myeloperoxidase catalyses the conversion of H2O2 and CI− to the cytotoxic agent HOCl. Stimulated neutrophils can release MPO into the extracellular environment and then may cause tissue injury through direct endothelial cells lysis. We showed that human umbilical vein endothelial cells (HUVEC) were capable of taking up active MPO. In presence of H2O2 (10−4 M), this uptake was accompanied by cell lysis. The cytolysis was estimated by the release of 51Cr from HUVEC and expressed as an index of cytotoxicity (IC). Dose dependent protection was obtained for CAZ concentrations ranging from 10−5 to 10−3 M;this can be attributed to inactivation of HOCl by the drug. This protection is comparable to that obtained with methionine and histidine, both of which are known to neutralize HOCl. This protection by CAZ could also be attributed to inactivation of H2O2, but when cytolysis was achieved with H2O2 or O2− generating enzymatic systems, no protection by CAZ was observed. Moreover, the peroxidation activity of MPO (action on H2O2) was not affected by CAZ, while CAZ prevented the chlorination activity of MPO (chlorination of monochlorodimedon). So, we concluded that CAZ acts via HOCl inactivation. These antioxidant properties of CAZ may be clinically useful in pathological situations where excessive activation of neutrophils occurs, such as in sepsis.http://dx.doi.org/10.1155/S0962935195000706 |
| spellingShingle | M. Mathy-Hartert G. Deby-Dupont C. Deby L. Jadoul A. Vandenberghe M. Lamy Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime Mediators of Inflammation |
| title | Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime |
| title_full | Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime |
| title_fullStr | Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime |
| title_full_unstemmed | Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime |
| title_short | Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime |
| title_sort | cytotoxicity towards human endothelial cells induced by neutrophil myeloperoxidase protection by ceftazidime |
| url | http://dx.doi.org/10.1155/S0962935195000706 |
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